KCC2 is an important K+-Cl- co-transporter that along with Na+-K+-2Cl- co-transporter, NKCC1 is largely responsible for the regulation of intracellular chloride concentration in neurons which determines whether the ionotropic GABAergic/glycinergic responses are depolarizing or hyperpolarizing. There are spatiotemporal differences in the intracellular chloride concentration in individual neurons which are attributable to a differential temporal and spatial activation of cation chloride co-transport mediated by KCC2 and NKCC1. Post-translational modulation of proteins is a fundamental cellular mechanism for such spatiotemporal regulation of protein activity. This thesis deals with the work that has been ongoing in our laboratory to understand the mechanisms of post-translational regulation of KCC2 function. In Study I, we have demonstrated a fast post-translational increase in KCC2 co-transport function in neonatal rat hippocampus after a single seizure episode. This TrkB-dependent effect was caused by an increased surface expression of KCC2. Study II deals with the establishment of a modified protease cleavage method for quantitative analysis of surface expression of proteins using a cold-adapted trypsin. This can serve as a fast and reliable procedure and can be easily applied to brain slice preparations as well as cell culture systems. In study II, we have also shown that KCC2 has a low surface expression in the rat hippocampus but a very fast turn-over rate of the plasmalemmal pool. Not surprisingly, modifications in the turn-over rate of the surface pool can be employed as a mechanism to regulate the surface expression of KCC2 and consequently its function. Study III deals with another post-translational cellular strategy to regulate KCC2 function in the rat hippocampus under patho-physiological conditions. While the KCC2 protein is quite stable in the rat hippocampus and has a slow turn-over rate under basal conditions, epileptiform activity and excitotoxicity can induce a rapid calpain-mediated cleavage of KCC2 with a consequent loss of its co-transport function.